Sökning: onr:"swepub:oai:DiVA.org:uu-461438" > Monitoring drug–tar...
Fältnamn | Indikatorer | Metadata |
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000 | 05909naa a2200577 4500 | |
001 | oai:DiVA.org:uu-461438 | |
003 | SwePub | |
008 | 211214s2022 | |||||||||||000 ||eng| | |
009 | oai:prod.swepub.kib.ki.se:150805658 | |
024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4614382 URI |
024 | 7 | a https://doi.org/10.1093/nar/gkac8422 DOI |
024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1508056582 URI |
040 | a (SwePub)uud (SwePub)ki | |
041 | a engb eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Al-Amin, Rasel A.,c Researcher,d 1983-u Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)abdal875 |
245 | 1 0 | a Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ |
264 | c 2022-10-03 | |
264 | 1 | b Oxford University Press,c 2022 |
338 | a electronic2 rdacarrier | |
520 | a Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to fixed adherent cells agreed with expectations from expression profiles of the cells. We also introduce a proximity ligation variant of TEMA to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug–target interactions at spatial resolution in protein arrays, cells and in tissues. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Medicinsk bioteknologi0 (SwePub)304012 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Medical Biotechnology0 (SwePub)304012 hsv//eng |
653 | a Biology with specialization in Molecular Biotechnology | |
653 | a Biologi med inriktning mot molekylär bioteknik | |
700 | 1 | a Johansson, Larsu Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet4 aut |
700 | 1 | a Abdurakhmanov, Eldar,d 1977-u Uppsala universitet,Biokemi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)eldab338 |
700 | 1 | a Landegren, Nils,d 1986-u Karolinska Institutet,Uppsala universitet,Klinisk diabetologi och metabolism,Center for Molecular Medicine, Department of Medicine (Solna), Science for Life Laboratory, Karolinska Institutet4 aut0 (Swepub:uu)nillan544 |
700 | 1 | a Löf, Lizau Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)lizlo931 |
700 | 1 | a Arngården, Linda,d 1984-u Uppsala universitet,Hematologi4 aut0 (Swepub:uu)linan615 |
700 | 1 | a Blokzijl, Andriesu Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)andbl969 |
700 | 1 | a Svensson, Richardu Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)ricsv977 |
700 | 1 | a Hammond, Maria,d 1984-u Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)marha169 |
700 | 1 | a Lönn, Peteru Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylära verktyg4 aut0 (Swepub:uu)pelon623 |
700 | 1 | a Haybaeck, Johannesu Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck; Diagnostic and Research Institute of Pathology, Medical University of Graz4 aut |
700 | 1 | a Kamali-Moghaddam, Masoodu Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)masookam |
700 | 1 | a Jenmalm Jensen, Annikau Karolinska Institutet4 aut |
700 | 1 | a Danielson, U. Helena,c Professor,d 1959-u Uppsala universitet,Biokemi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)helenads |
700 | 1 | a Artursson, Peru Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)perartur |
700 | 1 | a Lundbäck, Thomasu Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet4 aut |
700 | 1 | a Landegren, Ulfu Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)ulfland |
710 | 2 | a Uppsala universitetb Molekylära verktyg4 org |
773 | 0 | t Nucleic Acids Researchd : Oxford University Pressg 50:22, s. e129-e129q 50:22<e129-e129x 0305-1048x 1362-4962 |
856 | 4 | u https://doi.org/10.1093/nar/gkac842y Fulltext |
856 | 4 | u https://doi.org/10.21203/rs.3.rs-1109577/v1y Pre-print in full-text |
856 | 4 | u https://uu.diva-portal.org/smash/get/diva2:1620006/FULLTEXT02.pdfx primaryx Raw objecty fulltext:print |
856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-461438 |
856 | 4 8 | u https://doi.org/10.1093/nar/gkac842 |
856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:150805658 |
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